title: Endothelial activation biomarkers increase after HIV-1 acquisition: plasma vascular cell adhesion molecule-1 predicts disease progression.
abstract: OBJECTIVE
  We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters.
  
  
  METHODS
  HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition.
  
  
  METHODS
  Plasma levels of angiopoietin-1 and angiopoietin-2 (ANG-1, ANG-2) and soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were tested in stored samples from pre-infection, acute infection, and two chronic infection time points. We used nonparametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 < 200 cells/μl, stage IV disease, or antiretroviral therapy initiation) or death.
  
  
  RESULTS
  Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all postinfection periods assessed (P < 0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (P = 0.0001), and ANG-1 decreased in chronic infection (P = 0.0004). Among 228 participants followed over 1028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (adjusted hazard ratio 5.36, 95% confidence interval 1.99-14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels.
  
  
  CONCLUSIONS
  HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 postinfection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington 98104-2499, USA. grahamsm@u.washington.edu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Graham
authors.forename: Nimerta
authors.initials: N
authors.lastname: Rajwans
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Benson B A
authors.initials: BB
authors.lastname: Estambale
authors.forename: R Scott
authors.initials: RS
authors.lastname: McClelland
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
mesh_terms: D000328:Adult; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D019040:E-Selectin / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007630:Kenya; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D016019:Survival Analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; D019040:E-Selectin; C546936:SELE protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1